In the late 20(th) century, the treatment of cancer began to include its prevention. Today, compounds exist that will lower the risk of developing certain types of cancer. This has been demonstrated in studies where chemically induced tumor growth has been slowed or reversed. Anti-inflammatory compounds having chemopreventive activity are piroxicam, sulindac, aspirin, celecoxib and curcumin. The selective estrogen receptor modulators, tamoxifen and raloxifene, are beneficial in the prevention of estrogen dependent tumors. Retinoids, vitamin A derivatives, such as targretin and fenretinide are useful in the prevention of tumors. Compounds containing sulfur, such as sulforaphane and oltipraz, are even useful as radioprotective agents. The steroid dehydroepiandosterone can inhibit experimental carcinogenesis. All of these chemical classes provide a start for the medicinal chemist to design more effective chemopreventive agents. The biomarkers used to determine the chemopreventive activity of new compounds are quite often activities of enzymes. The identification of those individuals at high risk is still in its infancy and presents a troubling dilemma.
The brain remains an area where little corrective surgery can be performed and the reversal of damage is almost impossible. Recently, reports of agents offering neuroprotection have begun to appear in the literature. The concept of neuroprotection is the administration of some agent, which should reverse some of the damage or prevent further damage. Some agents offer protection against cell degeneration to the neuronal cells. Still other agents specifically protect the dopamine neurons and the retina. The majority of neuroprotective agents are antioxidants. An immunosuppressive calcineurin inhibitor, NOS inhibitor, sigma-1 modulator, AMPA antagonist and Ca2+ channel blocker have all shown neuroprotective activity. An estrogen agonist and two glycoprotein IIb/IIIa antagonists also exhibit neuroprotective activity. Most of the synthetic compounds presented were not originally designed as neuroprotective agents but were found to possess neuroprotective activity in later studies. Many of these compounds are biologically active natural products, either plant extracts or endogenous peptides/proteins. This review will present the most recent reports on these agents.
In an attempt to augment the efficacy of 7-chloro 4-aminoquinoline analogs and also to overcome resistance to antimalarial agents, we synthesized three cyclen (1,4,7,10-tetraazacyclododecane) analogs of chloroquine [a bisquinoline derivative, 7-chloro-4-(1,4,7,10-tetraaza-cyclododec-1-yl)-quinoline HBr, and a 7-chloro-4-(1,4,7,10-tetraaza-cyclododec-1-yl)-quinoline-Zn
SummaryIt has been shown that the most important inhibitor of plasmin is α2-antiplasmin, however, other protease inhibitors are able to inhibit this proteolytic enzyme as well. The contribution of the various protease inhibitors to the inhibition of plasmin in vivo has never been quantitatively assessed.To assess the relative contribution of the different protease inhibitors on the inhibition of plasmin we developed a series of sensitive immunoassays for the detection of complexes between plasmin and the protease inhibitors α2-antiplasmin, α2-macroglobulin, antithrombin III, α1antitrypsin and C1-inhibitor, utilizing monoclonal antibodies that are specifically directed against complexed protease inhibitors and a monoclonal antibody against plasmin.It was confirmed that α2-antiplasmin is the most important inhibitor of plasmin in vivo, however, complexes of plasmin with α2-macroglobulin, antithrombin III, α1antitrypsin- and C1-inhibitor were also detected. Particularly during activation of fibrinolysis complexes between plasmin and inhibitors other than α2-antiplasmin were detected. It was observed that during different situations the inhibition profile of plasmin was not constant e.g. in patients with diffuse intravascular coagulation plasma levels of plasmin-α1-antitrypsin and plasmin-C1-inhibitor were increased whereas in plasma from patients who were treated with thrombolytic agents complexes of plasmin with α2-macroglobulin and with antithrombin III were significantly elevated.In conclusion, we confirmed the important role of α2-antiplasmin in the inhibition of plasmin, however, in situations in which fibrinolysis is activated other protease inhibitors also account for the inhibition of plasmin in vivo. Further investigations to assess the role of the various protease inhibitors in the fibrinolytic system can be assisted by the assays described in this study.
This video presentation was created to show a method of harvesting the two most important highly vascular structures, not residing within the brain proper, that support forebrain function. They are the cerebral surface (superficial) vasculature along with associated meninges (MAV) and the choroid plexus which are necessary for cerebral blood flow and cerebrospinal fluid (CSF) homeostasis. The tissue harvested is suitable for biochemical and physiological analysis, and the MAV has been shown to be sensitive to damage produced by amphetamine and hyperthermia 1,2 . As well, the major and minor cerebral vasculatures harvested in MAV are of potentially high interest when investigating concussive types of head trauma. The MAV dissected in this presentation consists of the pial and some of the arachnoid membrane (less dura) of the meninges and the major and minor cerebral surface vasculature. The choroid plexus dissected is the structure that resides in the lateral ventricles as described by Oldfield and McKinley 3,4,5,6 . The methods used for harvesting these two tissues also facilitate the harvesting of regional cortical tissue devoid of meninges and larger cerebral surface vasculature, and is compatible with harvesting other brain tissues such as striatum, hypothalamus, hippocampus, etc. The dissection of the two tissues takes from 5 to 10 min total. The gene expression levels for the dissected MAV and choroid plexus, as shown and described in this presentation can be found at GSE23093 (MAV) and GSE29733 (choroid plexus) at the NCBI GEO repository. This data has been, and is being, used to help further understand the functioning of the MAV and choroid plexus and how neurotoxic events such as severe hyperthermia and AMPH adversely affect their function. Video LinkThe video component of this article can be found at https://www.jove.com/video/4285/ ProtocolAlthough not shown in the video, rats were first given an overdose of 300 mg/kg of pentobarbital, resulting in anesthesia in less than 3 min, and then killed by decapitation. Their brains were then rapidly but carefully removed from the skull and chilled in ice-cold normal saline for 5 min. It is important to let the brain cool for this amount of time prior to dissecting the MAV so that the MAV can be separated from the surface of the cortex (top of layer I). The brain was then placed in the bottom of a glass Petri dish resting on ice that was full (1 cm deep) of ice-cold normal saline or 0.1 M sodium phosphate-buffered saline pH=7.4. All the dissection is done with the brain for the most part immersed in saline. Removal of the Pineal Gland1. Place the brain dorsal side up (relative to the bottom of the Petri dish). The pineal gland is located at the most caudal ventral region between the two hemispheres just rostral to the cerebellum (pineal recess), and is just below or at the surface of the meninges over the colliculi. Remove the pineal gland first using two small bent tip forceps. It is pink in color like the cortex but is often surrounded in remnants o...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.